Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in...Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).展开更多
Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being s...Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic effi...Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.展开更多
Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,va...Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].展开更多
Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs a...Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation tran...Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.展开更多
White spot syndrome virus(WSSV) is an important viral pathogen that infects farmed penaeid shrimp, and the threat of Vibrio parahaemolyticus infection to shrimp farming has become increasingly severe. Viral and bacter...White spot syndrome virus(WSSV) is an important viral pathogen that infects farmed penaeid shrimp, and the threat of Vibrio parahaemolyticus infection to shrimp farming has become increasingly severe. Viral and bacterial cross or superimposed infections may induce higher shrimp mortality. We used a feeding method to infect L itopenaeus vannamei with WSSV and then injected a low dose of V. parahaemolyticus(WSSV+Vp), or we fi rst infected L. vannamei with a low-dose injection of V. parahaemolyticus and then fed the shrimp WSSV to achieve viral infection(Vp+WSSV). The effect of V. parahaemolyticus and WSSV co-infection on survival of L. vannamei was evaluated by comparing cumulative mortality rates between experimental and control groups. We also spread L. vannamei hemolymph on thiosulfate citrate bile salt sucrose agar plates to determine the number of V ibrio, and the WSSV copy number in L. vannamei gills was determined using an absolute quantitative polymerase chain reaction(PCR) method. L v My D88 and Lvakt gene expression levels were detected in gills of L. vannamei by real-time PCR to determine the cause of the different mortality rates. Our results show that(1) the cumulative mortality rate of L. vannamei in the WSSV+Vp group reached 100% on day 10 after WSSV infection, whereas the cumulative mortality rate of L. vannamei in the Vp+WSSV group and the WSSV-alone control group approached 100% on days 11 and 13 of infection;(2) the number of Vibrio in the L. vannamei group infected with V. parahaemolyticus alone declined gradually, whereas the other groups showed signifi cant increases in the numbers of Vibrio( P <0.05);(3) the WSSV copy numbers in the gills of the WSSV+Vp, Vp+WSSV, and the WSSV-alone groups increased from 10 5 to 10 7 /mg tissue 72, 96, and 144 h after infection, respectively. These results suggest that V. parahaemolyticus infection accelerated proliferation of WSSV in L. vannamei and vice versa. The combined accelerated proliferation of both V. parahaemolyticus and WSSV led to massive death of L. vannamei.展开更多
The pathogenicity of white spot syndrome virus （WSSV） to zooplankton species, rotifer Brachionus urceus （Linnaeus）, copepod Acartia clausi （Giesbrecht） and mysid shrimp Neomysis awatschensis （ Brandt ）, was es...The pathogenicity of white spot syndrome virus （WSSV） to zooplankton species, rotifer Brachionus urceus （Linnaeus）, copepod Acartia clausi （Giesbrecht） and mysid shrimp Neomysis awatschensis （ Brandt ）, was estimated by immersion challenge and virus - phytoplankton adhesion mute to investigate a potential new transmission mute of WSSV to zooplankton. WSSV succeeded in infecting these zooplankton species and nested-PCR revealed positive results for the virus - phytoplankton adhesion mute, whereas WSSV cannot infect zooplankton by immersion challenge. These results indicated that virus - phytoplankton adhesion route is a successful new transmission mute of WSSV to zooplankton and also implied that phytoplankton could be a carrier in WSSV transmission.展开更多
White Spot Syndrome Virus (WSSV) was purified from hemolymph of infected shrimp. After nucleic acid extraction from the purified virus particles, EcoR I digested fragments of the WSSV genome were cloned; three of thes...White Spot Syndrome Virus (WSSV) was purified from hemolymph of infected shrimp. After nucleic acid extraction from the purified virus particles, EcoR I digested fragments of the WSSV genome were cloned; three of these fragments were used as non radioactive probes labeled with DIG 11 dUTP. The probes hybridized in situ, with sections located in the nuclei of all WSSV infected tissues. The virus was detected in the gill, stomach, epidermis, and connective tissue and so on, but not detected in healthy shrimp tissues and epithelial cells of hepatopancreatic tubules of diseased shrimp.展开更多
White spot syndrome virus(WSSV)-resistant molecular markers were screened from the selectively bred new variety ‘Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting(HRM) tech...White spot syndrome virus(WSSV)-resistant molecular markers were screened from the selectively bred new variety ‘Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting(HRM) technique. After the artificial infection with WSSV, the first 96 dead shrimps and the last 96 surviving shrimps were collected, representing WSSV-susceptible and-resistant populations, respectively. The genotypes at well-developed 39 single nucleotide polymorphisms(SNPs) loci were obtained. As revealed in the Chi-square test, 3 SNPs, genotype A/A of contig C364-89 AT, genotype A/A of C2635-527 CA and genotype C/T of contig C12355-592 CT, were positively correlated with disease-resistance traits. Other 2 SNPs, genotype G/G of contig C283-145 AG and genotype C/C of contig C12355-592 CT, were negatively correlated. Moreover, analysis with Blast X program for disease-resistant SNPs indicated that 3 contigs, Contig283, Contig364 and Contig12355, matched to the functional genes of effector caspase of Penaeus monodon, peptide transporter family 1-like protein, and 40 S ribosomal protein S2 of Perca flavescens with high sequence similarity. The results will be helpful to provide theoretical and technical supports for molecular marker-assisted selective breeding of F. chinensis.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially i...Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.展开更多
A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(da...A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.展开更多
Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional va...Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses,whereas messenger RNA(mRNA)vaccines have demonstrated significant advantages due to their short development periods,straightforward production,and low costs.After the outbreak of the COVID-19 pandemic,multiple mRNA vaccines,including Pfizer-BioNTech and Moderna,rapidly received emergency use authorization,validating their feasibility.The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikóand Drew Weissman,underscoring the efficacy of mRNA vaccine technology.In 2024,the U.S.Food and Drug Administration(FDA)approval of Moderna's respiratory syncytial virus(RSV)mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation.This review article summarizes the design,clinical research,and future challenges of mRNA vaccines for respiratory viruses,delving into antigen design,mRNA delivery systems,and advancements in vaccines for multiple respiratory viruses,including innovations in self-amplifying mRNA and circular mRNA vaccines.Additionally,the development of combination vaccines is underway,aiming to provide protection against multiple viruses through a single administration.Despite the significant progress in mRNA vaccine development,challenges remain regarding raw material costs,stability,and delivery efficiency.In the future,with technological advancements and the accumulation of clinical experience,the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized,thereby enhancing their safety and efficacy.展开更多
AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected p...AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.展开更多
The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this...The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei （LvPT） was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigenTM design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at -27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA （4 pg per shrimp） was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection （hpi）. Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.展开更多
基金supported by the National Key Research and Development Program of China (2021YFD1800200)the National Natural Science Foundation of China (32170539)。
文摘Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).
基金supported by the Natural Science Foundation of Heilongjiang Province,China (YQ2022C040)。
文摘Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金Supported by the earmarked fund for CARS(No.CARS-48)the National Natural Science Foundation of China(No.32202964)。
文摘Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.
文摘Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].
文摘Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金financially supported by the National Natural Science Foundation of China(82127802,22374157)Strategic Priority Research Program,CAS(XDB0540000,XDC0170000)CAS Youth Interdisciplinary Team(JCTD-2022-13).In addition,Xin Zhou acknowledges the support from the Tencent Foundation through the XPLORER PRIZE.
文摘Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.
基金Supported by the National Basic Research Program of China(973 Program)(No.2012CB114405)the Special Foundation Under the Construction Program for the“Taishan Scholarship”of Shandong Province of Chinathe Program for Chinese Outstanding Talents in Agricultural Scientific Research
文摘White spot syndrome virus(WSSV) is an important viral pathogen that infects farmed penaeid shrimp, and the threat of Vibrio parahaemolyticus infection to shrimp farming has become increasingly severe. Viral and bacterial cross or superimposed infections may induce higher shrimp mortality. We used a feeding method to infect L itopenaeus vannamei with WSSV and then injected a low dose of V. parahaemolyticus(WSSV+Vp), or we fi rst infected L. vannamei with a low-dose injection of V. parahaemolyticus and then fed the shrimp WSSV to achieve viral infection(Vp+WSSV). The effect of V. parahaemolyticus and WSSV co-infection on survival of L. vannamei was evaluated by comparing cumulative mortality rates between experimental and control groups. We also spread L. vannamei hemolymph on thiosulfate citrate bile salt sucrose agar plates to determine the number of V ibrio, and the WSSV copy number in L. vannamei gills was determined using an absolute quantitative polymerase chain reaction(PCR) method. L v My D88 and Lvakt gene expression levels were detected in gills of L. vannamei by real-time PCR to determine the cause of the different mortality rates. Our results show that(1) the cumulative mortality rate of L. vannamei in the WSSV+Vp group reached 100% on day 10 after WSSV infection, whereas the cumulative mortality rate of L. vannamei in the Vp+WSSV group and the WSSV-alone control group approached 100% on days 11 and 13 of infection;(2) the number of Vibrio in the L. vannamei group infected with V. parahaemolyticus alone declined gradually, whereas the other groups showed signifi cant increases in the numbers of Vibrio( P <0.05);(3) the WSSV copy numbers in the gills of the WSSV+Vp, Vp+WSSV, and the WSSV-alone groups increased from 10 5 to 10 7 /mg tissue 72, 96, and 144 h after infection, respectively. These results suggest that V. parahaemolyticus infection accelerated proliferation of WSSV in L. vannamei and vice versa. The combined accelerated proliferation of both V. parahaemolyticus and WSSV led to massive death of L. vannamei.
基金Funding for this research was provided by the National Natural Science Foundation of China under contract No. 30371111； the National ＂973＂ Project of China under contract No. G1999012011；the National＂ 863＂ Program of China under contract No. 2002AA648010 ； the Tenth National Five Year Major Program of China under contract No. 2001BAS05B.
文摘The pathogenicity of white spot syndrome virus （WSSV） to zooplankton species, rotifer Brachionus urceus （Linnaeus）, copepod Acartia clausi （Giesbrecht） and mysid shrimp Neomysis awatschensis （ Brandt ）, was estimated by immersion challenge and virus - phytoplankton adhesion mute to investigate a potential new transmission mute of WSSV to zooplankton. WSSV succeeded in infecting these zooplankton species and nested-PCR revealed positive results for the virus - phytoplankton adhesion mute, whereas WSSV cannot infect zooplankton by immersion challenge. These results indicated that virus - phytoplankton adhesion route is a successful new transmission mute of WSSV to zooplankton and also implied that phytoplankton could be a carrier in WSSV transmission.
文摘White Spot Syndrome Virus (WSSV) was purified from hemolymph of infected shrimp. After nucleic acid extraction from the purified virus particles, EcoR I digested fragments of the WSSV genome were cloned; three of these fragments were used as non radioactive probes labeled with DIG 11 dUTP. The probes hybridized in situ, with sections located in the nuclei of all WSSV infected tissues. The virus was detected in the gill, stomach, epidermis, and connective tissue and so on, but not detected in healthy shrimp tissues and epithelial cells of hepatopancreatic tubules of diseased shrimp.
基金supported by the Taishan Scholar Program for Seed Industrythe Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02)National Natural Science Foundation of China(No.31372523)
文摘White spot syndrome virus(WSSV)-resistant molecular markers were screened from the selectively bred new variety ‘Huanghai No. 2' of Fenneropenaeus chinensis using unlabeled-probe high-resolution melting(HRM) technique. After the artificial infection with WSSV, the first 96 dead shrimps and the last 96 surviving shrimps were collected, representing WSSV-susceptible and-resistant populations, respectively. The genotypes at well-developed 39 single nucleotide polymorphisms(SNPs) loci were obtained. As revealed in the Chi-square test, 3 SNPs, genotype A/A of contig C364-89 AT, genotype A/A of C2635-527 CA and genotype C/T of contig C12355-592 CT, were positively correlated with disease-resistance traits. Other 2 SNPs, genotype G/G of contig C283-145 AG and genotype C/C of contig C12355-592 CT, were negatively correlated. Moreover, analysis with Blast X program for disease-resistant SNPs indicated that 3 contigs, Contig283, Contig364 and Contig12355, matched to the functional genes of effector caspase of Penaeus monodon, peptide transporter family 1-like protein, and 40 S ribosomal protein S2 of Perca flavescens with high sequence similarity. The results will be helpful to provide theoretical and technical supports for molecular marker-assisted selective breeding of F. chinensis.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
文摘Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.
基金Natural science foundation of Inner Mongolia(2024LHMS06018)The basic scientific research funding for directly affiliated universities in the Inner Mongolia(JY20250094)。
文摘A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.
基金Grants from the Ministry of Science and Technology of the People's Republic of China,Grant/Award Number:2021YFA1300301 and 2018YFA0507101National Natural Science Foundation of China,Grant/Award Number:31730054 and 31770900Beijing Natural Science Foundation,Grant/Award Number:5212016。
文摘Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses,whereas messenger RNA(mRNA)vaccines have demonstrated significant advantages due to their short development periods,straightforward production,and low costs.After the outbreak of the COVID-19 pandemic,multiple mRNA vaccines,including Pfizer-BioNTech and Moderna,rapidly received emergency use authorization,validating their feasibility.The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikóand Drew Weissman,underscoring the efficacy of mRNA vaccine technology.In 2024,the U.S.Food and Drug Administration(FDA)approval of Moderna's respiratory syncytial virus(RSV)mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation.This review article summarizes the design,clinical research,and future challenges of mRNA vaccines for respiratory viruses,delving into antigen design,mRNA delivery systems,and advancements in vaccines for multiple respiratory viruses,including innovations in self-amplifying mRNA and circular mRNA vaccines.Additionally,the development of combination vaccines is underway,aiming to provide protection against multiple viruses through a single administration.Despite the significant progress in mRNA vaccine development,challenges remain regarding raw material costs,stability,and delivery efficiency.In the future,with technological advancements and the accumulation of clinical experience,the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized,thereby enhancing their safety and efficacy.
基金Supported by the Self-funded Research Project of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z2016325).
文摘AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.
基金Supported by the National Basic Research Program of China(973 Program)(No.2012CB114403)the China Agriculture Research System-47(CARS-47)
文摘The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei （LvPT） was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigenTM design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at -27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA （4 pg per shrimp） was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection （hpi）. Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.
